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One-gene method makes safer human stem cells

The goal of curing diseases like Parkinson’s using cells generated from a patient’s own body has come a step closer. Researchers have successfully reprogrammed human nerve cells back to an embryo-like state using just one gene.

Embryonic stem cells are pluripotent – they can develop into any of the body’s cell types – but they are in short supply because they can only be harvested from a donated egg or embryo, and for ethical reasons most countries have laws restricting their use.

In 2006, Shinya Yamanaka and his colleagues at Kyoto University in Japan successfully made mouse cells pluripotent by reprogramming skin cells into a state like embryo cells.

To do this they used retroviruses to insert four genes – known as “factors” – into the cells’ DNA.

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Yamanaka’s team repeated the trick a year later with human cells. The problem is, using genes and retroviruses in this way increases the risk of the cell becoming cancerous, not just because tinkering with DNA has that effect, but also because two of the four factors are known to cause cancer.

Four, two, one

The race was on to make these promising cells in a safe way. Hans Schöler‘s team at the Max Planck Institute for Molecular Biomedicine in Münster, Germany, has been working to achieve pluripotency using fewer factors. Last year, the team managed it with the two factors that don’t cause cancer; now they’ve simplified the recipe further, doing it with just one.

“Remarkably, it turns out that three of these four essential factors are already expressed in human neural stem cells – although not in skin cells – so we only needed to add one factor, OCT4,” says Boris Greber, a member of the team.

Cells from neural tissue are much easier to reprogram than skin cells and are less prone to mutations, Greber says. It’s much harder to get a sample of neural stem cells than skin cells, though&colon; Greber says it can be done by extracting the cells from the dental pulp of teeth.

Clinical ban

Inserting even one gene into the chromosome of a cell still permanently modifies its DNA, so this new method will remain a laboratory tool and will not be allowed in the clinic.

But the researchers hope it will help them improve methods for producing embryonic stem cells. “Ideally, we will be able to find a chemical that does the same job of expressing the factor without the need for a gene,” Greber says.

That technique doesn’t involve inserting genes, so it shouldn’t raise the cancer risk, but it is far less efficient. “Without stable intervention using viruses, the frequency of reprogramming goes down and you have to wait a long time,” Greber says. “We don’t have the perfect method yet.”